Breast cancer is the most frequently diagnosed cancer in women and is also the leading cause of cancer related deaths among women worldwide, with 1.7 million new cases being diagnosed and more than 500,000 deaths occurring in 2012. Breast cancer treatment is dependent upon multimodal therapy with surgery being a primary component, especially for early stage cancers. Mastectomy (total removal of the breast) was the most common procedure choice for newly diagnosed breast cancer patients until the 1980s when studies revealed that lumpectomy, the far less disfiguring option, was shown to have the same 10 year survival rate as mastectomy. Despite this fact, approximately 25-50% of patients eligible for breast conservation therapy (BCT) will choose mastectomy over lumpectomy. A substantial concern of BCT patients is whether or not negative margins will be obtained in the initial surgery. Negative margins are achieved when no cancer cells are present on or near (usually within 5-10 mm) the border of the excised tissue and are considered necessary for a successful lumpectomy. Unfortunately, the current re-excision rates due to positive margins average 20-40% and range from 5-70%. Failure to achieve negative margins can result in the delay of radiation treatment, increase risk for local recurrence, cause psychological and physical stress on the patient, compromise cosmetic results, and increase cost.
The high re-excision rates arise from the difficulty in localizing tumor boundaries intra-operatively and lack of real time information on the presence of residual disease. The challenge in determining surgical margins intraoperatively is that geometric and spatial cues are quickly lost in the surgical presentation. Equally confounding is that valuable diagnostic images are acquired in a significantly different breast presentation than the typical surgical setup. Diagnostic and biopsy information are driven by mammography and preoperative MR images in which the patient is standing or lying prone with pendant breasts, while surgical presentation is in the supine position.
An example of this challenge is displayed in FIGS. 1A-1C, showing that the breast undergoes significant shape change between the prone and supine positions causing the tumor to deform and change location. FIGS. 1A and 1C are axial slices of T1-weighted THRIVE sequence MR images in the prone and supine positions with ovals designating the same tumor in the same axial slice. FIG. 1B shows the intraoperative presentation. As is readily apparent from FIGS. 1A-1C, the changes in patient setup cause the breast tissue, and thus the tumor, to move relative to the MR images. Thus, preoperative MR images have limited value when attempting to locate a tumor intraoperatively.
Current localization strategies used in the operating room (OR) include intraoperative ultrasound, wire guided approaches, and radio-guided occult lesion localization. Prospective studies report that wire guide localization results in positive margins in 38-43% of patients undergoing BCT. Intraoperative ultrasound (iUS) has been shown to improve BCT, but iUS is limited by the fact that only 50% of non-palpable tumors are visible by ultrasound in the breast. The shortcomings of radio-guided occult lesion localization are that the radioisotope must be accurately placed into the tumor and diffusion of the radiotracer into surrounding tissue decreases accuracy of the tumor location. In view of the foregoing, there is a need for accurate intraoperative localization of preoperatively identified tumors and other targets in breast tissues.